JP7396798B2 - Composition for promoting intestinal butyrate production - Google Patents

Description

TECHNICAL FIELD The present invention relates to a composition for promoting the production of butyric acid in the intestines, and food, drink, or pharmaceutical products using the same.

Adjusting the intestinal environment is important for disease prevention and health maintenance. Short-chain fatty acids produced by intestinal bacteria are not only used as an energy source for epithelial cells, but also have various functions such as suppressing inflammation and suppressing blood sugar rise. Water-soluble dietary fiber is important for the production of short-chain fatty acids, and inulin, a type of fructan, is known as a water-soluble dietary fiber.
Patent Document 1 discloses a synergistic composition for treating diabetes that combines inulin, sulfonylurea, etc.

JP2017-226672A

As in Patent Document 1, the effects of combinations of inulin and other compounds have been gradually reported, but the effects of combinations of inulin and other dietary fibers on short-chain fatty acid production derived from intestinal bacteria have not been studied. It has not been fully clarified yet.
An object of the present invention is to provide a composition for promoting butyric acid production in the intestines, and food, drink, or pharmaceutical products containing the same.

As a result of intensive research aimed at solving the above problems, the present inventors discovered that the production of butyric acid in the intestine was promoted by combining inulin and cellulose, and thus completed the present invention. That is, the present invention includes the following inventions.

[1] A composition for promoting intestinal butyric acid production containing inulin and cellulose.
[2] A food or drink containing the composition according to [1].
[3] A pharmaceutical product comprising the composition according to [1].

According to the present invention, a composition for promoting butyric acid production in the intestine, and a food/drink or pharmaceutical product using such a composition can be obtained.

It is a figure showing cellulose, inulin, and butyric acid production amount regarding cellulose and inulin.

The composition for promoting intestinal butyric acid production of the present invention (hereinafter also referred to as "composition of the present invention") is characterized by containing inulin and cellulose.

Inulin typically plays an important role as a prebiotic, and many animals, including humans, do not have inulin hydrolase, so it reaches the large intestine without being absorbed. The microflora in the large intestine includes bacteria that secrete inulinase, an enzyme that hydrolyzes inulin, and Bifidobacteria are particularly known as beneficial bacteria. Therefore, when food containing inulin is ingested, beneficial bacteria such as Bifidobacterium preferentially increase and the proliferation of harmful bacteria is suppressed. In addition, organic acids such as lactic acid increase during the fermentation process of inulin, which has an intestinal regulating effect.

In the present invention, a composition in which inulin further contains cellulose has an advantageous effect of promoting butyric acid production in the intestines.

In the present invention, "inulin" is a straight-chain form in which D-fructofuranose is polymerized with β2→1 glycosidic bonds among fructans, which are known as water-soluble dietary fibers and are polysaccharide polymers of fructose with glucose at the end. Contains "linear inulin" which is a fructan. Furthermore, "inulin" in the present invention also includes "branched inulin" which is a branched fructan having a β2→1 glycosidic bond and at least one β2→6 glycosidic bond.

Linear inulin usually has a chain length in the range of 2 to 100, preferably in the range of 2 to 60, with an average chain length of usually 5 to 20, and at least 90% of the bonds in inulin are β2→1. It is a glycosidic bond. Such linear inulin can be, for example, Frutafit (registered trademark) or Raftiline (registered trademark) in the case of chicory-derived inulin, and can be, for example, Fuji FF (registered trademark) in the case of using inulin produced by enzymatic synthesis. Can be used.

On the other hand, branched chain inulin is known to be abundant in agave, a succulent plant that is the raw material for tequila (J. Agric. Food Chem., (2003) 51 (27), pp 7835-7840, J. Agric. Food Chem., (2006) 54 (20), pp 7832-7839, etc.). Branched chain inulin in the present invention is not particularly limited, but can be obtained, for example, from the above-mentioned agave by the conventional method described in WO 07/142306 pamphlet, etc., and typically, it is obtained by shredding from piña, which is the stem part of agave. It is included in processed products that have undergone juice extraction, filtration, purification, concentration, powder drying, etc. Such a processed product is also called agaba inulin.

Inulin in the present invention can take various forms such as powder, solution, or syrup, and may be used as a binder for foods by increasing its viscosity.

Cellulose in the present invention is a natural polymer in which β-glucose molecules are linearly polymerized through glycosidic bonds, and can typically be ingested as insoluble dietary fiber from foods such as vegetables and fruits. Such cellulose may be contained in the form of food containing cellulose, or may be contained in the form of extracted and purified cellulose powder, and is not particularly limited.

The content of inulin and cellulose is not limited as long as it contains an effective amount that exhibits the desired effect, but the weight ratio of inulin and cellulose based on total dietary fiber is 25:75 to 75:25 ( %) is sufficient. As for the total amount, the total weight of powdered inulin and cellulose should normally be about 1 to 50 g per day for humans. As a method for quantifying total dietary fiber, Megazyme's Total Dietary Fiber Assay Kit, which complies with AOAC991.43, can be used.

The composition for promoting intestinal butyrate production of the present invention synergistically promotes the production of butyric acid, a short-chain fatty acid that is a metabolite thereof, by being digested and fermented mainly by intestinal bacteria in the human large intestine. I can do it. Generally, in the human large intestine, intestinal bacteria produce short-chain fatty acids when they ferment dietary fiber, which plays an essential role in maintaining health. In humans, three types of short-chain fatty acids are known as typical short-chain fatty acids: acetic acid, propionic acid, and butyric acid. The part of the human body where short-chain fatty acids are produced is the large intestine, which is home to many intestinal bacteria, and the produced short-chain fatty acids are absorbed into the body from the large intestine. Among the absorbed short-chain fatty acids, butyric acid, whose production is promoted in the present invention, is used as an energy source for colon epithelial cells. Additionally, approximately 60% of the body's immune cells are concentrated in the intestine, and it is said that an imbalance in the immune system in the intestine, especially an excessive immune response, can affect the whole body, but butyric acid has the ability to suppress excessive immune responses. It has been suggested that it has the effect of increasing T cells (Nature (2013) 504, pp 446-450). Furthermore, since short chain fatty acids themselves are acidic components, the production of short chain fatty acids creates a slightly acidic intestinal environment. Weak acidity suppresses the activity of enzymes produced by bad bacteria, making it difficult to produce carcinogenic secondary bile acids and harmful putrefaction products, and maintains a healthy intestinal environment by regulating the intestines.

The composition of the present invention can also be used as a medicine or food or drink for humans or animals. In this specification, food and drink for animals is also referred to as feed.

The pharmaceutical agent in the present invention may be an intestinal butyric acid production promoter containing the composition of the present invention. The dosage forms of the above pharmaceuticals include, for example, oral preparations such as tablets, capsules, granules, powders, syrups, dry syrups, solutions, and suspensions, and enteral preparations such as inhalants, transdermal preparations, and suppositories. Examples include parenteral preparations such as preparations, drips, and injections. The above-mentioned liquid preparations such as solutions and suspensions may be in the form of being dissolved or suspended in water or other suitable medium immediately before administration, and the above-mentioned tablets and granules may be coated on the surface by a well-known method. You can leave it there. Further, the above-mentioned injection may be a solution of sterile distilled water or sterile physiological saline containing a solubilizing agent as necessary.

In addition to the composition of the present invention, the pharmaceutical product of the present invention may contain various pharmaceutically acceptable carriers, such as excipients, stabilizers, and other additives, as necessary. Alternatively, it may further contain other medicinal ingredients such as various vitamins, minerals, herbal medicines, etc. The pharmaceutical product can be produced by adding the above-mentioned carrier and other medicinal ingredients to the composition of the present invention in accordance with a conventional method.

The food/beverage products or feeds in the present invention include health foods, functional food/beverage products, and food/drinks for specified health uses that contain the composition of the present invention and are labeled as intended to promote the production of butyric acid in the intestine, as the case may be. It can also be used as food and drink for the sick, feed for livestock, racehorses, ornamental animals, etc., pet food, etc.

The form of food/drinks and feed in the present invention is not particularly limited, and includes all forms in which the composition of the present invention can be blended. For example, the form may be solid, semi-solid, or liquid, and may include various forms such as tablets, chewable tablets, powders, capsules, granules, drinks, gels, syrups, and liquid diets for enteral feeding. .

Examples of specific foods and drinks include tea drinks such as green tea, oolong tea, and black tea, coffee drinks, soft drinks, jelly drinks, sports drinks, milk drinks, carbonated drinks, fruit juice drinks, lactic acid bacteria drinks, fermented milk drinks, and powdered drinks. , cocoa drinks, alcoholic drinks, beverages such as purified water, spreads such as butter, jam, furikake, margarine, mayonnaise, shortening, cream, dressings, breads, rice, noodles, pasta, miso soup, tofu, milk, Yogurt, soups or sauces, bakery items (bread, pies, cakes, cookies, biscuits, crackers, etc.), sweets (biscuits, cookies, chocolate, candy, cakes, ice cream, chewing gum, tablets, etc.), nutritional supplements ( Examples include supplements in the form of pills, tablets, jelly preparations, capsules, etc., granola-like cereals, granola-like snake bars, cereal bars), and the like.

Since the feed in the present invention can be used in almost the same composition and form as the above-mentioned food and drink products, the description regarding the food and drink products in this specification can be similarly applied to the feed.

The food and drink products and feeds of the present invention include the composition of the present invention, other food and drink materials used in the production of food and drink products and feeds, various nutrients, various vitamins, minerals, amino acids, various oils and fats, and various additives. It can be produced according to a conventional method by adding flavor components, sweeteners, acidulants such as organic acids, surfactants, pH adjusters, stabilizers, antioxidants, pigments, flavors, etc.). Alternatively, the food, drink, or feed according to the present invention can be produced by blending the composition of the present invention into the food, drink, or feed that is commonly eaten.

The content of the composition of the present invention in the pharmaceutical product, food/beverage product, or feed of the present invention may be any amount that provides the desired effect of promoting intestinal butyric acid production, and may be determined by the dosage form of the drug, the form of the food/beverage product, administration, or intake. The total weight of powdered inulin and cellulose should normally be about 1 to 50 g per day for humans, although the amount may be changed as appropriate depending on the species, symptoms, age, sex, etc. of the individual.

The present invention will be specifically explained below with reference to Examples and Comparative Examples, but the scope of the present invention is not limited thereby.

[Sample preparation]
As samples, 3 g of cellulose (sample name: "Cell"), 3 g of inulin (sample name: "IQ"), 1.5 g of cellulose, and 1.5 g of inulin (also: "Cell + IQ") were prepared. . Cellulose was purchased from Fujifilm Wako Pure Chemical Industries, and inulin was Frutafit IQ (registered trademark) (Sensus).

[Preparation of fecal suspension]
In order to reproduce the intestinal flora that mimics the human large intestine, we adopted an artificial intestinal tract model using feces from pigs (4-5 months old). The fecal suspension was prepared by adding and mixing 10 times as much physiological saline to frozen pig feces, and then filtering the mixture using a strain bag (Eiken Chemical).

[In vitro intestinal fermentation test]
For in vitro enteric fermentation testing, Bio Jr. 8 culture device (Able) was used. A culture tank containing 80 mL of distilled water and a solution prepared by dissolving 4.8 g of Nutrient Broth (Difco Laboratories) in 100 mL of distilled water were each sterilized at 121° C. for 15 minutes. After sterilization and cooling, 20 mL of the fecal suspension was mixed into a culture tank and cultured overnight. The setting conditions of the culture apparatus were a temperature of 37° C. and a stirrer rotation speed of 400 rpm. It was set so that an alkaline solution (2N sodium hydroxide) was automatically dripped when the pH in the culture tank fell below 5.5. Additionally, in order to maintain the inside of the culture tank in an anaerobic state, it was filled with carbon dioxide gas.
After culturing overnight, 20 mL of a solution in which Nutrient Broth was dissolved and the sample were added to the culture tank. After culturing for 48 hours, the culture solution was collected and centrifuged to obtain a culture supernatant.

[Measurement of short chain fatty acids]
For the measurement of short chain fatty acids, an ultra-high performance liquid chromatograph (NexeraX2, Shimadzu Corporation) was used, and the analysis conditions were as shown in Table 1. 1 mL of 0.5N perchloric acid was added to 450 μL of the culture supernatant, left to stand for 5 minutes, and then centrifuged. The resulting supernatant was filtered through an HPLC pretreatment filter and used as a measurement sample. Butyric acid was identified by comparing the retention times of the measurement sample and the standard solution, and quantified by comparing the peak areas.

[Example 1]
When the test was conducted as described above and the amount of butyric acid in the culture solution of each sample addition group was measured, the results shown in FIG. 1 and Table 2 were obtained. A significant increase in the amount of butyric acid in the culture solution was observed in the Cell+IQ addition group compared to the IQ addition group or the Cell addition group.
The synergistic effect of these combinations was calculated using the following formula.
<Synergy> = XY/((X/2)+(Y/2))
(In the formula, X is the amount of short chain fatty acids of cellulose (Cell) alone, Y is the amount of short chain fatty acids of inulin (IQ) alone, and XY is the amount of short chain fatty acids when each sample is added in combination. ], XY and X or Y have the same total dietary fiber content, so X or Y has a single short chain fatty acid content halved)
From the above calculation formula, the synergistic effect of the Cell+IQ addition group was calculated from each value in Table 2 as 2.35/((0.57/2)+(0.75/2)), which was 3.6 It has doubled. Therefore, a synergistic effect in Cell+IQ was confirmed, and it was shown that the combination of inulin and cellulose promoted butyric acid production from intestinal flora.

Claims (4)

A composition for promoting intestinal butyric acid production, comprising inulin derived from chicory and having an average chain length of 5 to 20, and cellulose, wherein the weight ratio of inulin to cellulose in the composition is 1. :3 to 3:1 (excluding the composition for promoting intestinal butyric acid production containing inulin and cellulose derived from soybean polysaccharide). The composition for promoting intestinal butyric acid production according to claim 1, wherein the weight ratio is 1:1. A food or drink product for promoting intestinal butyric acid production, comprising the composition according to claim 1 or 2 . A pharmaceutical for promoting intestinal butyrate production, comprising the composition according to claim 1 or 2 .

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